Investigations of the neuronal mechanisms of drug actions are necessary for discerning the neurobiological basis of euphoria and drug abuse. Many abused pharmacological agents have several commonalities, including self-administration by non-humans in experimental settings, discriminative stimulus properties that can result in state-dependent learning and the disruption of schedule-controlled behavior. Many studies that have investigated neuronal activity mediating drug reinforcement have used self-administration procedures. Selective dopaminergic or noradrenergic neurotoxin lesions of the nucleus accumbens by receptor antagonists delivered into this area influenced responding maintained by both stimulant and opiate self-administration. However, the changes reported in drug intake and the rate of responding do not necessarily indicate a change in the reinforcing efficacy of a drug. This research project proposes investigations of the involvement of several neurotransmitter systems in the behavioral mechanisms of action of cocaine and d-amphetamine. The behavioral effects of four specific neurotoxin lesions of the nucleus accumbens that destroy either dopaminergic, noradrenergic, serotonergic, or intrinsic and efferent fibers will be studied. Intracranial injections of reversible gamma aminobutyric acid, dopamine, 5-hydroxytryptamine and opiate receptor antagonists delivered directly into the nucleus accumbens will also be used to delineate the neurobiological substrates of the behavioral effects of cocaine and heroin. The behavioral mechanisms that will be investigated include alteration of schedule-controlled behavior, changes in discriminative stimulus properties, and a dose-preference procedure which provides rate-free measure of reinforcing efficacy. These studies will determine the involvement of several neuronal systems located in the nucleus accumbens in modulating the behavioral effects of drugs, thus providing information on the neurobiological basis of these effects.